Saudi Journal of Kidney Diseases and Transplantation

: 2017  |  Volume : 28  |  Issue : 6  |  Page : 1404--1407

Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: An unusual association

Ishwarya Annamalai, G Chandramohan, ND Srinivasa Prasad, Edwin Fernando, S Sujith 
 Department of Nephrology, Government Stanley Hospital, Chennai, Tamil Nadu, India

Correspondence Address:
Ishwarya Annamalai
Department of Nephrology, Government Stanley Hospital, Chennai, Tamil Nadu


Anti-glomerular basement membrane (anti-GBM) disease is a systemic autoimmune disorder characterized by circulating IgG antibodies (rarely IgA and IgM) to the carboxyterminal, noncollagenous 1 (NC1) domain of type IV collagen of GBM also known as Goodpasture antigen. Patients typically present with rapidly progressive glomerulonephritis (RPGN) and pulmonary hemorrhage in the presence of which it is referred to as Goodpasture’s disease. Anti-GBM disease has been reported to coexist with pauci-immune antineutrophil cytoplasmic autoantibody-positive glomerulonephritis and membranous glomerulopathy. The sequential or concurrent presentation of anti-GBM disease with IgA nephropathy has been rarely described. We herein report a case of a 22-year-old female who presented with RPGN, and renal biopsy revealed crescentic glomerulonephritis with strong linear IgG (+2) staining of GBM and extensive mesangial IgA (+3) deposits. The patient was treated with three pulses of IV methylprednisolone followed by oral steroids. Plasmapheresis and cytotoxic agents were not included in the therapeutic armamentarium as the patient had no pulmonary hemorrhage and biopsy revealed established chronic changes. The association of anti-GBM disease with IgA nephropathy could open up new vistas on the implication of these IgA mesangial deposits in the pathogenesis and prognosis of anti-GBM disease.

How to cite this article:
Annamalai I, Chandramohan G, Srinivasa Prasad N D, Fernando E, Sujith S. Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: An unusual association.Saudi J Kidney Dis Transpl 2017;28:1404-1407

How to cite this URL:
Annamalai I, Chandramohan G, Srinivasa Prasad N D, Fernando E, Sujith S. Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: An unusual association. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2022 Sep 29 ];28:1404-1407
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Full Text


Classical Goodpasture’s disease is a relatively rare monophasic illness with pulmonary hemorrhage and crescentic glomerulonephritis (CSGN) that is distinguished from other forms of CSGN by its intense and diffuse linear staining of IgG, especially IgG1 and IgG4 involving glomerular basement membrane (GBM). The hallmark of this entity is the circulating anti-GBM antibodies directed against the NC1 domain of alpha 3 chain of type IV collagen found in GBM and alveolar basement membrane. Antibodies are detected in approximately 95% of patients by immunoassays using various forms of purified or recombinant substrates. Anti-GBM antibody titer, however, does not always correlate well with the manifestation or course of renal disease. Anti-GBM antibodies have been identified to coexist in a proportion of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis usually pANCA[1] and infrequently in patients with membranous nephropathy.[2] We report a rare case of anti-GBM disease with coexisting IgA nephropathy. A total of four cases have been reported in literature so far, with one among them in the posttransplant setting.[3],[4],[5],[6]

 Case Report

A 22-year-old female was admitted in our institution in December 2015 with the presenting complaints of gross hematuria, bilateral swelling of legs, facial puffiness, and reduced urine output for one week. History was significant for an episode of gross hematuria that resolved in two days, one month before the present admission. She denied a history of fever, skin rash, or joint pain. There was no family history of renal disease. The patient was comfortable at rest, and physical examination was unremarkable except for pallor, bilateral pitting pedal edema and an elevated blood pressure of 170/100 mm Hg. Her cardiovascular, abdominal, and respiratory system examinations were normal.

Urinalysis showed 3+ red blood cells and 3+ protein. Urine spot protein/creatinine ratio was 6.8. Urine culture was sterile. Her Hb was 8.6 g/dL, and serum creatinine at the time of admission was 1.9 mg/dL showing a progressive increase to 3.2 mg/dL over the next one week. Serum C3 was 123.5 mg/dL and C4 was 27.60 mg/dL (within normal reference range). Antibody profile was negative for anti-nuclear antibodies, anti-double stranded DNA, pANCA, and cANCA. Qualitative assay of anti-GBM antibody by immunoblot method was positive. Quantitative anti-GBM antibody assay by Autostat™ II Anti-GBM (Hycor Biomedical Ltd., California, USA), a solidphase enzyme-linked immunosorbent assay for the semiquantitative determination of specific IgG antibodies in serum was 96 U/mL was used in our patient. (Kit results were interpreted by <15 U/mL as negative, 15–20 equivocal, and >20 positive). Serology for hepatitis B surface antigen and anti-hepatitis C virus antibody was negative. Ultrasonogram showed normal-sized kidneys and computed tomography chest was normal.

Renal biopsy performed in view of rapidly progressive glomerulonephritis yielded cortex containing 10 glomeruli for light microscopy, of which three were globally sclerotic and the remaining seven glomeruli had fibrous to fibrocellular crescents in all [Figure 1]. Direct immunofluorescence demonstrated dominant IgA (+3) [Figure 2] and C3 (+1) staining over mesangium with linear positivity for IgG (+2) along GBM [Figure 3].{Figure 1}{Figure 2}{Figure 3}

The patient was treated with three pulses of IV methylprednisolone 500 mg/day followed by oral prednisolone 0.5 mg/kg/day. As renal biopsy showed predominant chronic changes, intense immunosuppression protocol was not adopted weighing the potential risks of immunosuppression versus the low possibility of salvaging her renal function. During the course of her illness in hospital, the patient did not develop pulmonary hemorrhage and continues to have nondialysis-dependent renal failure.


Ours is a rare case report of anti-GBM disease coexisting with IgA nephropathy. IgA nephropathy is the most common mesangioproliferative glomerulonephritis with abnormal O-glycosylation of the IgA1 hinge region being the key pathogenic factor and the kidney an innocent bystander. A galore of disease associations with IgA nephropathy has been described.[7] Our patient had no related symptoms of IgA nephropathy such as an upper respiratory tract infection preceding hematuria, liver disease, or inflammatory bowel disease. About one-third of patients with anti-GBM antibodies have detectable ANCA usually myeloperoxidase ANCA. This “double positivity” may have important therapeutic and prognostic implications with patients requiring longer duration of immunosuppression and some studies showing better renal outcomes even in dialysis-dependent renal failure compared to patients with anti-GBM disease alone.[8] Our patient had no clinical/serological evidence of ANCA-associated vasculitis nor pulmonary hemorrhage during her hospital stay. We seek to substantiate the category of crescentic glomerulonephritis and the temporal profile of these two entities in our patient with the available literature reviews on crescentic glomerulonephritis.[9] As the crescents were all of the same chronological age with involvement of nearly 100% of the sampled glomeruli, an anti-GBM antibody-mediated crescentic glomerulonephritis is more likely than an immune complex-mediated crescentic glomerulonephritis that rarely affects more than 50% of glomeruli. This distinction may be of prognostic value as anti-GBM disease is the most aggressive form of crescentic glomerulonephritis, with the highest frequency of renal insufficiency followed by ANCA-associated vasculitis and then by immune complex-mediated crescentic glomerulonephritis.[9] In our case, it is possible that the anti-GBM disease was superimposed on a preexisting smoldering IgA nephropathy and had brought the patient to clinical attention. We speculate that the immune complexes deposited in the glomeruli and the release of inflammatory mediators could trigger the initiation of anti-GBM disease through exposure of cryptic antigens. Zhao Cui et al reported that the association of glomerular immune complexes with anti-GBM disease did not lead to a benign prognosis.[10] We opted for a less aggressive immunosuppression regimen in our patient considering the morphology of the biopsy. Patient’s creatinine stabilized at around 3.0 mg/dL at the time of discharge and is on regular follow up. Whether there exists any pathogenic affiliation between IgA deposits in the mesangium and anti-GBM disease or they are mere coeffectors remains to be determined.


We place on record our appreciation to Dr. Anila Abraham Kurien, Director of Center for Renal and Urological Pathology Pvt., Ltd., Anna Nagar, Chennai, for the help rendered in the pathological diagnosis of this patient.

Conflict of interest: None declared.


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